1362926 玖、發明說明 【發明所屬之技術領域】 本發明係有關於皮膚具有持續保護水份之效果，良好 使用性之薄型化水性貼劑。 【先前技術】 先行之糊劑係於不織布等支撐體上廣泛塗佈以水溶性 φ高分子做爲主體之膏體。膏體厚度爲700~ 1 5 00g/m2後， 對於皮膚之黏著性佳，且，初期膏體含水量亦高，具良好 皮膚之保水效果者。 . 惟，先行之糊劑爲發揮黏著力，務必有一定之厚度， 貼於關節等動作多的部份將無法伏貼，或與衣服摩擦後， 出現剝落。又，長時間貼黏後，產生保水能力消失之問題 。爲解決此等問題，且爲改良物性經時的安定性，製造適 切亦被期待糊劑之薄型化者。 φ 本發明使用先行公知之糊劑製造技術，嘗試試作薄型 化水性貼劑，惟，其具如下之缺點。 亦即，先行糊劑使用支撐體透氣性高之不織布、織布 等者，而，薄型化時，貼黏中藉由體溫其糊劑中之水份被 蒸發，皮膚無法充份被覆水份。 又，同時蒸發水份引起膏體之乾燥’糊劑對於皮膚之 黏著力降低之同時，另一藉由皮膚黏著部之膏體固化後， 對於皮膚附著度過高，於剝離時出現疼痛、造成皮膚輕度 損傷。 -4- 1362926 支撐體透氣性低之薄膜，或其以黏著劑、熱熔接法貼 黏不織布者其柔軟性、均勻性均差，與糊劑之膏體相互親 和性不足，對於貼黏時，貼黏部位活動時走位，造成剝離 ，而剝離時，產生薄膜受損，殘留膏體於皮膚等問題點。 特別是，先行糊劑並未重視支撐體之構成與膏體成份 之構成及其組合。如：先行糊劑若多量塗佈膏體（ 700~ 1 5 00g/m2)，則具理想之黏著力，惟，此並非於薄型 φ化水性貼劑絕對理想設計基礎下所製作者，此單純進行薄 型化（塗佈量150〜5 00g/m2)時，其製造難易度、品質、 皮膚貼附性及其經時安定性，製造成本面均無法實用化。 _ 【發明內容】 本發明之目的係提供一種於皮膚可持續保護水份之效 果，具良好使用性之薄型化水性貼劑者。 本發明者針對支撐體之構成與適於支撐體膏體成份之 φ構成進行精密研討之結果發現，絡合天然纖維與軟質性塑 膠纖維之複合纖維中以熱熔接軟質性塑膠樹脂之纖維薄膜 (具薄膜層之纖維）所構成之支撐體，或共有軟質部與硬 質部之塑膠所形成之纖維中以熱熔接軟質部與硬質部之塑 膠樹脂纖維薄膜所構成之支撐體中將水、保濕劑、聚丙燃 酸及/或其鹽類、纖維素衍生物、難溶性多價金屬鹽、pH 調製劑以適當比例進行混合後，將調製pH爲4〜6之膏體 以150~500g/m2之塗工量廣範圍塗佈後，可解決上述問題 點，取得薄型化水性貼劑，進而完成本發明。 1362926 亦即，本發明之特徵係於支撐體上層合黏著劑層（膏 體）之貼劑者，該支撐體由絡合天然纖維與軟質塑膠纖維 之複合纖維中熱熔接軟質塑膠樹脂之纖維薄膜，或於共有 軟質部與硬質部之塑膠所形成纖維中熱熔接共有軟質部與 硬質部之塑膠樹脂之纖維薄膜所成之薄型化水性貼劑。 更具體例係有關該黏著劑層（膏體）以水、保濕劑、 聚丙烯酸及/或其鹽所成之黏著附與劑、纖維素衍生物所 φ成之黏著力調整劑、難溶性金屬鹽所成之交聯劑及pH調 整劑做爲必須構成成份之薄型化水性貼劑者。 . 【實施方式】 [發明實施之最佳形態] 本發明用於支撐體之絡合天然纖維與軟質塑膠纖維複 合纖維係使天然纖維與軟質塑膠纖維以1:9〜9:1之比爲宜 ，較佳者爲2:8〜8:2，特別以3:7~7:3爲最佳，其機械性 •外觀重量以 5~50g/m2，較佳爲 7〜40g/m2，特別以 10〜3 Og/m2之範圍進行絡合形成者爲最理想。 本發明之支撐體係於此複合纖維中使軟質塑膠樹脂以 薄膜狀厚度3〜35 μπι，較佳爲5〜30 μιη，特別佳者爲8〜25 μηι之範圍被熱熔接後所取得者。此時，使用非單一複合 纖維者，適當調整纖維比例後，於熱熔接時，其複合纖維 之軟質塑膠纖維部呈強行熔接於軟質塑膠薄膜之狀態，同 時，足量之天然纖維未熔接薄膜而露出表面，其結果，與 膏體之親和性極高。 -6- 1362926 本明細書所使用之天然纖維中含有源於天然物之半合 成或再生纖維者，如：人造絲、棉等例。 做爲軟質塑膠纖維例者如：聚乙烯、聚丙烯、乙烯甲 基丙烯酸甲酯、氯化乙烯基等例，特別以聚乙烯、聚丙烯 爲較佳者。 做爲軟質塑膠樹脂例者如：聚乙烯、乙烯甲基丙烯酸 甲酯、聚丙烯等例，特別以聚乙烯、乙烯甲基丙烯酸甲酯 φ爲較佳者。 複合纖維之構成中，天然纖維之比例超出90w/w%時 (軟質塑膠纖維之比例不足1 〇% )則複合纖維與薄膜部份 之熔接不足，且，軟質塑膠纖維之比例超出90w/w% (天 然纖維比例不足1 〇w/w% )則所露出纖維量不足，而降低 與膏體之親和性，特別是於剝離時，出現殘留膏體於皮膚 之問題。 不論天然纖維與軟質塑膠纖維之配合比，其複合纖維 φ之外觀重量不足5 g/m2時，與膏體之親和性降低，而，超 出50 g/m2則複合纖維太多，膏體埋入纖維黏著力降低， 無法取得薄型化之貼劑。 被熔接之軟質塑膠樹脂薄膜之厚度不足3 μΐη時，與 複合纖維之熔接不足，使用此之貼劑於剝離時易出現支撐 體之破損。超出3 5 μηι時，使用此貼劑，未薄型化，特別 是對於貼附部位之活動，降低隨從性，易出現剝離。 又，做爲本發明之其他支撐體者，共有軟質部與硬質 部之塑膠所形成之纖維中可使用熱熔接共有軟質部與硬質 1362926 部之塑膠樹脂纖維薄膜者。 共有軟質部與硬質部之塑膠所形成之纖維其機械性外 觀重量以10〜80 g/m2，較佳者15~70 g/m2，特別佳爲 20~60 g/m2之範圍下絡合後被形成之。 本發明之其他支撐體係於此纖維中使共有硬質部與軟 質部塑膠呈薄膜厚度爲7〜70 μπι，較佳爲10〜60 μηι，特 別佳者15~45 μιη之範圍下藉由熱熔接後取得。此時，熔 鲁接機械之設定雖重要而更以非爲單一，纖維部與塑膠樹脂 之同時，使用共有軟質部與硬質部之塑膠，使外觀重量、 厚度等適正化後，可取得薄型化水性貼劑有用之支撐體。 總之，熱熔接時，含纖維與薄膜之軟質部相互強型熔接， 惟，同時’纖維與薄膜中存在硬質部後，妨礙纖維過度置 入薄膜，足夠量之纖維露出表面，提高與膏體之親和性。 做爲構成纖維及薄膜之共有軟質部與硬質部塑膠者， 以高分子彈性體爲宜，特別以聚醯胺彈性體、聚酯彈性體 Φ爲更佳。 共有軟質部與硬質部之塑膠所形成之纖維外觀重量不 足1 0 g/m2時，則支撐體與膏體相互親和性降低，特別是 貼劑剝離時，出現殘留膏體於皮膚。反之，超出80 g/m2 時，則纖維太多，膏體埋入纖維之黏著力下降，而未能取 得具足夠黏著力之薄型化貼劑。 共有被熔接硬質部與軟質部之塑膠薄膜厚度不足7 μηι時，則與纖維之熔接較弱，使用此之貼劑則於剝離時 易出現支撐體之破損。反之，超出70 μιη時，則支撐體之 -8- 1362926 柔軟性不足，使用此貼劑則對於貼附部位活動時，降低隨 從性·，易出現剝離。 本發明黏著劑層之成份，亦即膏體成份係以水、保濕 劑、聚丙烯酸及/或其鹽類、纖維素衍生物、難溶性多價 金屬鹽、及pH調整劑做爲必須構成成份者，此等勻勻混 合後，以150〜5 00g/m2之重量塗佈於本發明支撐體後，可 製作與膏體親和性充足之薄型化水性貼劑。 φ 本發明針對支撐體之構成，以及適於該支撐體之膏體 構成成份進行精密硏討後結果所取得者，膏體成份及其配 合比不在下記之範圍時，則所取得之膏體物性變得極端、 黏著力及保形性（強度）惡化，甚至與本發明支撐體之親 和性爲不足者。 以下針對膏體構成成份進行說明。 黏著劑成份之水係爲溶解聚丙烯酸及/或其鹽類、纖 維素衍生物之媒體者，且，附與皮膚濕潤之成份者。其配 φ 合量以20〜70w/w%爲宜，較佳者爲25〜60w/w%，特別佳 者爲30~50w/w%。當配合量不足20w/w%則聚丙烯酸衍生 物及纖維素衍生物將無法充份溶解呈不均勻者，膏體之黏 著力、保形性均不足，且’降低對皮膚之保水性。反之’ 配合量超出7〇w/w%則膏體之保形性變弱，爲不理想者。 保濕劑係爲提高對皮膚之保濕效果者’同時進行調整 膏體之保形性。做爲保濕劑之例者如：甘油、1 ’ 3 - 丁二 醇' 丙二醇、聚丙二醇、D-山梨聚醇、聚乙二醇4 00等例 ，其中特別以甘油、1’ 3 -丁二醇、丙二醇爲較佳者。其 ** 9 - 1362926 配合量以20~60w/w%者宜，較佳者爲25〜55 w/w%，特別 以30〜50 w/w%爲最佳。當配合量不足20 w/w%時，則膏 體之保形性將不足，且，降低對皮膚之保濕性。反之，配 合量超出60 w/w%則其他配合劑，特別是水之配合量將不 足，造成膏體之黏著力、保形性（強度）不足而不理想。 聚丙烯酸及/或其鹽類係做爲黏著附與劑，藉由溶於 水時之增黏機能與交聯體形成後，進行提高膏體之黏著力 φ者。做爲聚丙烯酸及其鹽類例者如：聚丙烯酸、聚丙烯酸 鈉、聚丙烯酸部份中和物等例，可使用其中1種或2種以 上之組合者。其配合量以 3~25 w/w %者宜，較佳者爲 5〜20 w/w%，特別以7~ 15 w/w%爲最佳。當配合量不足3 w/w%則降低膏體之黏著力，反之，配合量超出25 w/W% 則水中出現不溶部份、膏體不均、黏著力無法保持恆定。 纖維素衍生物係做爲黏著調整劑，藉由溶於水時之增 黏機能可進行調整膏體之保形性。做爲纖維素衍生物者如 •:羧甲基纖維素鈉、羥丙基纖維素、羥甲基纖維素等例， 可使用其中1種或2種以上之組合者，特別又以羧甲基纖 維素鈉爲較佳者。其配合量以1 ~20 w/w%者宜，較佳者爲 2〜1 5 w/w%，特別以3~1 0 w/w%爲最佳。當配合量不足1 w/w%時，則黏性低，無法維持膏體之保形性。反之，配 合量超出20 w/w%則水中出現不溶部份，膏體呈不均狀， 無法保持保形性之恆定。 難溶性多價金屬鹽係做爲交聯劑者，形成聚丙烯酸衍 生物之交聯體後，維持膏體之保形性者。做爲難溶性多價 -10- 1362926 金屬鹽者如：二羥基鋁胺基乙酸酯、矽酸鋁酸鎂、氫氧化 鋁、合成水滑石等例，其中特別以二羥基鋁胺基乙酸酯、 合成水滑石爲較佳者。其配合量爲0.01〜5 W/W%者宜，較 佳者爲0.01 5〜3.5 w/w%，特別以0.03〜2 w/w%爲最佳。當 配合量不足〇.〇1 w/w%則交聯體形成不全，膏體保形性惡 化。反之，配合量超出5 w/w%則交聯體形成變多，黏著 性變差。 PH調整劑係爲調整膏體之pH者。做爲pH調整劑 例者如：酒石酸、乳酸、蘋果酸等例。本發明貼劑係意圖 長時間貼於皮膚者，爲恐皮膚藉由強酸或強鹽基物質之過 度受傷，務必維持膏體於適當之pH者，此時理想之pH 以4〜6爲宜。因應變動膏體pH之聚丙烯酸等物質之配合 量，該 pH 調整劑務必以 0.1〜5 w/w%，較佳者爲 0.25~3.5 w/w%，特以0.5〜2 w/w%爲最佳範圍進行適當調 整配合之。 於本發明之支撐體進行塗佈，層合之膏體重量以 150〜500g/m2爲宜，較佳者爲 200〜450 g/m2，特別以 250〜400 g/m2爲最佳。 該製作之本發明貼劑只要依其適用部位，切成適當形 狀、尺寸使用即可。 該膏體亦可配合具治療效果之藥物。該藥物只要可安 定配合於膏體成份者即可，未特別限定，如：消炎鎭痛劑 、皮質類固醇劑（去炎松、戊酸倍他米松等）：抗組織胺 劑、止癢劑、抗高血壓劑 '麻醉劑、抗真菌劑、抗癲癎劑 -11 - 1362926 、冠狀血管擴張劑、激素劑 '肌肉弛緩劑、局部刺激劑、 抗病毒劑（阿昔洛維等）等例。 本發明貼劑因含有水份，因此，膏體本身或配合具療 效之藥物時，爲使該藥物安定化，亦可添加安定化劑、防 腐劑等。 本發明貼劑亦可用於覆蓋（保護）創傷部位者。 φ [實施例] 以下例舉實施例進行說明之，惟，本發明未受限於此 等實施例者。 [實施例1] 以表1所示實施例1之膏體成份爲基準，依以下次序 ，製作貼劑。 於甘油（39 w/w% )中加入聚丙烯酸鈉（4 w/w% )、 •羧甲基纖維素鈉（4.5 w/w%)、羥丙基纖維素（〇.5 w/w% )、二羥基鋁胺基乙酸酯（0.06 w/w% )進行分散之（分 散液 1)。精製水（42.44 w/w% )中加入酒石酸（1.5 w/w% )與聚丙烯酸（5 w/w% )進行溶解後，此液進行攪 拌之同時，於此漸次加入分散液1，進行攪拌至均勻塊狀 爲止做成膏體。 於表1所示實施例1之支撐體成份所成之支撐體中塗 佈此膏體呈膏體重量爲3 00 g/m2後，以聚酯薄膜覆蓋黏 著面，呈20cm x2 0cm之正方形狀進行穿孔後，做成貼劑 -12- 1362926 ，將此置入包裝袋內進行密封後，保存於室溫。 [實施例2-4及比較例1〜4] 以表1及表2所載組成爲基準，與實施例1同法依序 製作實施例2~4及比較例1〜4之貼劑。1362926 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明 发明[Prior Art] The first paste is applied to a support such as a non-woven fabric and is coated with a water-soluble φ polymer as a main body. After the thickness of the paste is 700~1 5 00g/m2, the adhesion to the skin is good, and the initial paste has a high water content, and the skin has good water retention effect. However, in order to exert adhesion, the first paste must have a certain thickness. The parts that are attached to the joints and other movements will not be able to lie on the surface, or after rubbing against the clothes, peeling off. Moreover, after sticking for a long time, the problem of water retention capacity disappears. In order to solve these problems, and to improve the stability of the physical properties over time, it is also expected to be suitable for the thinner of the paste. φ The present invention attempts to test a thinned aqueous patch using the prior art known paste manufacturing technique, but has the following disadvantages. That is, the first paste is a non-woven fabric or a woven fabric having a high gas permeability of the support, and in the case of thinning, the moisture in the paste is evaporated by the body temperature during sticking, and the skin cannot be sufficiently covered with water. Moreover, at the same time, evaporation of water causes the paste to dry. 'The adhesion of the paste to the skin is reduced, and the other is cured by the paste of the skin adhesion portion. The adhesion to the skin is too high, and pain occurs during peeling. Mild skin damage. -4- 1362926 A film with a low gas permeability of the support, or which is adhered to the nonwoven fabric by an adhesive or a heat fusion method, has poor flexibility and uniformity, and has insufficient affinity with the paste of the paste. When the adhesive portion moves, it causes the peeling, and when peeling, the film is damaged, and the residual paste is applied to the skin and the like. In particular, prior pastes do not pay attention to the composition of the support and the composition and combination of the paste components. For example, if the paste is applied in a large amount (700~1 500 00g/m2), it has an ideal adhesion. However, this is not the basis of the absolute ideal design of the thin φ water-based patch. When the thickness is reduced (coating amount: 150 to 500 g/m2), the ease of manufacture, quality, skin adhesion, and stability over time are not practical. SUMMARY OF THE INVENTION An object of the present invention is to provide a thinned aqueous patch which has a good effect on the skin and which can effectively protect moisture. The inventors of the present invention have made a close study on the composition of the support and the φ composition suitable for the composition of the support paste, and found that the composite fiber of the natural fiber and the soft plastic fiber is thermally fused to the fiber film of the soft plastic resin ( a support body composed of a fiber layer of a film layer, or a fiber formed of a plastic portion having a soft portion and a hard portion, wherein a water and a moisturizer are contained in a support body formed by thermally fusing a soft resin portion and a hard portion of a plastic resin fiber film. After the polypropionic acid and/or its salts, the cellulose derivative, the poorly soluble polyvalent metal salt, and the pH adjusting agent are mixed in an appropriate ratio, the paste having a pH of 4 to 6 is prepared to be 150 to 500 g/m 2 . After coating a wide range of coatings, the above problems can be solved, and a thinned aqueous patch can be obtained, and the present invention can be completed. That is, the present invention is characterized in that a patch for laminating an adhesive layer (paste) on a support body is a fiber film of a heat-fusible soft plastic resin in a composite fiber of a composite natural fiber and a soft plastic fiber. Or a thinned water-based patch formed by a fiber film of a plastic resin having a soft portion and a hard portion in a fiber formed of a plastic having a soft portion and a hard portion. More specifically, the adhesive layer (paste) is an adhesive agent made of water, a moisturizing agent, polyacrylic acid, and/or a salt thereof, an adhesion regulator made of a cellulose derivative, and a poorly soluble metal. The cross-linking agent and the pH adjusting agent formed by the salt are used as a thin-formed aqueous patch which is a constituent component. [Embodiment] [Best Mode for Carrying Out the Invention] The composite fiber of the present invention is used for the composite fiber of the support body and the soft plastic fiber composite fiber. The ratio of the natural fiber to the soft plastic fiber is preferably 1:9 to 9:1. Preferably, it is 2:8~8:2, especially 3:7~7:3, and the mechanical and appearance weight is 5~50g/m2, preferably 7~40g/m2, especially It is most desirable to form a complex formation in the range of 10 to 3 Og/m2. In the support system of the present invention, the soft plastic resin is obtained by heat-welding the soft plastic resin in a film thickness of 3 to 35 μm, preferably 5 to 30 μm, particularly preferably 8 to 25 μm. In this case, when a non-single composite fiber is used, the fiber ratio is appropriately adjusted, and when the heat fusion is performed, the soft plastic fiber portion of the composite fiber is forcibly welded to the soft plastic film, and at the same time, a sufficient amount of the natural fiber is not welded to the film. The surface is exposed, and as a result, the affinity with the paste is extremely high. -6- 1362926 The natural fibers used in this book contain semi-synthetic or regenerated fibers derived from natural materials, such as rayon and cotton. Examples of the soft plastic fiber include polyethylene, polypropylene, ethylene methyl methacrylate, vinyl chloride, and the like, and polyethylene or polypropylene is preferred. Examples of the soft plastic resin include polyethylene, ethylene methyl methacrylate, and polypropylene. Particularly, polyethylene or ethylene methyl methacrylate φ is preferred. In the composition of the composite fiber, when the ratio of the natural fiber exceeds 90 w/w% (the ratio of the soft plastic fiber is less than 1%), the fusion of the composite fiber and the film portion is insufficient, and the ratio of the soft plastic fiber exceeds 90 w/w%. (The ratio of the natural fiber is less than 1 〇w/w%) The amount of the exposed fiber is insufficient, and the affinity with the paste is lowered, and particularly when peeling, the problem of the residual paste on the skin occurs. Regardless of the blend ratio of natural fiber to soft plastic fiber, when the apparent weight of composite fiber φ is less than 5 g/m2, the affinity with the paste is lowered, and if it exceeds 50 g/m2, the composite fiber is too much, and the paste is buried. The fiber adhesion is lowered, and a thinned patch cannot be obtained. When the thickness of the soft plastic resin film to be welded is less than 3 μΐη, the fusion with the composite fiber is insufficient, and the use of the patch tends to cause damage to the support at the time of peeling. When the thickness exceeds 3 5 μηι, the patch is not thinned, especially for the activity of the attached portion, and the follow-up property is lowered, and peeling is likely to occur. Further, as the other support of the present invention, a fiber formed of a soft portion and a hard portion may be a heat-welded composite soft portion and a hard 1362926 plastic resin fiber film. The fibers formed by the soft portion and the hard portion have a mechanical appearance weight of 10 to 80 g/m2, preferably 15 to 70 g/m2, particularly preferably 20 to 60 g/m2. Was formed. In the other supporting system of the present invention, the common hard portion and the soft portion plastic have a film thickness of 7 to 70 μm, preferably 10 to 60 μm, particularly preferably 15 to 45 μm, by heat welding. Acquired. In this case, the setting of the melt-bonding machine is important, and it is more than a single one. When the fiber part and the plastic resin are used together, the plastic of the soft part and the hard part is used, and the weight and thickness of the surface are moderated, and the thickness can be reduced. A useful support for aqueous patches. In short, in the case of heat welding, the soft portion of the fiber-containing film and the film are strongly welded to each other, but at the same time, after the hard portion is present in the fiber and the film, the fiber is prevented from being excessively inserted into the film, and a sufficient amount of the fiber is exposed to the surface to improve the paste. Affinity. As the composite soft portion and the hard portion plastic constituting the fiber and the film, a polymer elastomer is preferable, and a polyamine elastomer or a polyester elastomer Φ is particularly preferable. When the weight of the fiber formed by the soft portion and the hard portion is less than 10 g/m2, the affinity between the support and the paste is lowered, and in particular, when the patch is peeled off, the residual paste appears on the skin. On the other hand, when it exceeds 80 g/m2, the fiber is too much, and the adhesive force of the paste embedded in the fiber is lowered, and a thin type patch having sufficient adhesive force cannot be obtained. When the thickness of the plastic film of the welded hard portion and the soft portion is less than 7 μηι, the fusion with the fiber is weak, and when the patch is used, the support is easily broken at the time of peeling. On the other hand, when it exceeds 70 μm, the support -8- 1362926 is insufficient in flexibility, and when the patch is used, the adherence is reduced when the attached portion is active, and peeling is likely to occur. The composition of the adhesive layer of the present invention, that is, the paste component is composed of water, a humectant, polyacrylic acid and/or a salt thereof, a cellulose derivative, a poorly soluble polyvalent metal salt, and a pH adjuster. After uniformly mixing and applying the mixture to the support of the present invention at a weight of 150 to 500 g/m 2 , a thin aqueous patch having sufficient affinity for the paste can be produced. φ The present invention is directed to the constitution of the support, and the results obtained after the precise composition of the paste constituents of the support are obtained, and the paste composition and the mixture ratio are not in the range of the following, and the obtained paste physical properties are obtained. It becomes extremely extreme, the adhesion and shape retention (strength) deteriorate, and even the affinity with the support of the present invention is insufficient. The following describes the composition of the paste. The water component of the adhesive component is a medium which dissolves the polyacrylic acid and/or its salts and cellulose derivatives, and is attached to the moisturizing component of the skin. The amount of φ is preferably 20 to 70 w/w%, preferably 25 to 60 w/w%, and particularly preferably 30 to 50 w/w%. When the compounding amount is less than 20 w/w%, the polyacrylic acid derivative and the cellulose derivative may not be sufficiently dissolved to be uneven, and the adhesiveness and shape retention of the paste are insufficient, and the water retention property to the skin is lowered. On the other hand, if the amount of compounding exceeds 7〇w/w%, the shape retention of the paste becomes weak, which is not ideal. The moisturizer is used to improve the moisturizing effect on the skin while adjusting the shape retention of the paste. Examples of the humectant include glycerin, 1 '3-butanediol' propylene glycol, polypropylene glycol, D-sorbitol, polyethylene glycol 4 00, etc., among which glycerin, 1' 3 - butyl Alcohol and propylene glycol are preferred. The amount of ** 9 - 1362926 is preferably 20~60w/w%, preferably 25~55 w/w%, especially 30~50 w/w%. When the compounding amount is less than 20 w/w%, the shape retaining property of the paste will be insufficient, and the moisturizing property to the skin will be lowered. On the other hand, if the compounding amount exceeds 60 w/w%, the amount of other compounding agents, particularly water, will be insufficient, resulting in insufficient adhesion and shape retention (strength) of the paste. The polyacrylic acid and/or its salt is used as an adhesive adhesion agent, and the adhesion of the paste is improved by forming a viscosity-increasing function and a crosslinked body when dissolved in water. As examples of the polyacrylic acid and its salts, such as polyacrylic acid, sodium polyacrylate, and polyacrylic acid partial neutralizing agents, one or more of them may be used. The compounding amount is preferably 3 to 25 w/w%, preferably 5 to 20 w/w%, and particularly preferably 7 to 15 w/w%. When the blending amount is less than 3 w/w%, the adhesive force of the paste is lowered. Conversely, if the blending amount exceeds 25 w/W%, the insoluble portion appears in the water, the paste is uneven, and the adhesive force cannot be kept constant. The cellulose derivative is used as an adhesion adjuster to adjust the shape retention of the paste by the viscosity-enhancing function when dissolved in water. As a cellulose derivative such as: carboxymethylcellulose sodium, hydroxypropylcellulose, hydroxymethylcellulose, etc., one or a combination of two or more thereof may be used, particularly a carboxymethyl group. Cellulose sodium is preferred. The compounding amount is preferably from 1 to 20 w/w%, preferably from 2 to 15 w/w%, and particularly preferably from 3 to 10 w/w%. When the compounding amount is less than 1 w/w%, the viscosity is low, and the shape retaining property of the paste cannot be maintained. On the other hand, if the compounding amount exceeds 20 w/w%, an insoluble portion appears in the water, and the paste is uneven, and the conformality cannot be maintained constant. The poorly soluble polyvalent metal salt is used as a crosslinking agent to form a crosslinked body of a polyacrylic acid derivative, and the shape retaining property of the paste is maintained. As a poorly soluble multivalent -10 1362926 metal salt such as: dihydroxy aluminum amine acetate, magnesium silicate aluminate, aluminum hydroxide, synthetic hydrotalcite, etc., especially dihydroxy aluminum amine acetate Synthetic hydrotalcite is preferred. The compounding amount is preferably 0.01 to 5 W/W%, more preferably 0.01 to 3.5 w/w%, and particularly preferably 0.03 to 2 w/w%. When the amount of compounding is insufficient 〇.〇1 w/w%, the crosslinked body is incompletely formed, and the shape retaining property of the paste is deteriorated. On the other hand, when the amount exceeds 5 w/w%, the formation of the crosslinked body increases, and the adhesiveness deteriorates. The pH adjuster is used to adjust the pH of the paste. As a pH adjuster, for example, tartaric acid, lactic acid, malic acid, and the like. The patch of the present invention is intended to be applied to the skin for a long time. In order to prevent the skin from being excessively damaged by a strong acid or a strong salt-based substance, it is necessary to maintain the paste at an appropriate pH. The pH is preferably 4 to 6 at this time. The pH adjuster must be 0.1 to 5 w/w%, preferably 0.25 to 3.5 w/w%, especially 0.5 to 2 w/w%, depending on the amount of the polyacrylic acid or the like which changes the pH of the paste. The best range is adjusted appropriately. The coated body of the present invention is coated, and the laminated paste preferably has a weight of 150 to 500 g/m2, preferably 200 to 450 g/m2, particularly preferably 250 to 400 g/m2. The patch of the present invention to be produced may be used in an appropriate shape and size depending on the site to which it is applied. The paste can also be combined with a therapeutic drug. The drug is not particularly limited as long as it can be stably formulated with a paste component, such as an anti-inflammatory analgesic agent, a corticosteroid (de-inflammatory pine, betamethasone valerate, etc.): an antihistamine, an antipruritic, Antihypertensive agents 'anesthetic agents, antifungal agents, antiepileptic agents -11 - 1362926, coronary vasodilators, hormonal agents 'muscle relaxants, topical stimulators, antiviral agents (acyclovir, etc.) and the like. Since the patch of the present invention contains water, when the paste itself or a therapeutic drug is formulated, a stabilizer, an antiseptic, or the like may be added in order to stabilize the drug. The patch of the present invention can also be used to cover (protect) a wound site. φ [Examples] The following examples are given to illustrate the invention, but the invention is not limited to the examples. [Example 1] A patch was prepared in the following order based on the paste composition of Example 1 shown in Table 1. Add sodium polyacrylate (4 w/w%), sodium carboxymethylcellulose (4.5 w/w%), hydroxypropylcellulose (〇.5 w/w%) to glycerol (39 w/w%) Dihydroxyaluminum acetate (0.06 w/w%) was dispersed (dispersion 1). After adding tartaric acid (1.5 w/w%) and polyacrylic acid (5 w/w%) to the purified water (42.44 w/w%), the solution was stirred while gradually adding the dispersion 1 and stirring. The paste is formed into a uniform block shape. After applying the paste to the support body of the composition of the first embodiment shown in Table 1, the paste has a paste weight of 300 g/m2, and the adhesive surface is covered with a polyester film to have a square shape of 20 cm x 2 0 cm. After perforation, a patch of -12-1362926 was prepared, placed in a packaging bag, sealed, and stored at room temperature. [Example 2-4 and Comparative Examples 1 to 4] The patches of Examples 2 to 4 and Comparative Examples 1 to 4 were produced in the same manner as in Example 1 on the basis of the compositions shown in Tables 1 and 2.
-13- 1362926-13- 1362926
比較例3 (w/w%) 43.24 一 卜 - 0.06 (N d (N 〇 m 〇 舞 60% 28% 12% | 25 g / m 2 1 ss 3g m 劉 10 μ m rt — 350 g/m" 比較例2 50.44 ο m cs m cs <N 〇 0.06 一 m d 60% 28% 12% 1 18g/mz 1 80 μ m 400 g / m z 比較例1 | 42.44 ON m m 々 iTi w-> Ο 0.06 in 100% 1 〇 1 3g/m2 1 15 μ m cn — 300 g / m2 實施例3 43.24 沄 in 卜 m — in (N 0.06 (N iT) d <N d m d 30% 70% 25 g / m ^ | 10 μ m tT ! 230 g/m" | 實施例2 50.44 <N ο m fS (N <N d 0.06 一 m d 鐽 <D 50% 50% | l〇g/mJ | HOT m 概 20 μ m *T) 350 gfm1 N N »Λ v〇 yrt ε E m E 、 鹿 (N d d S 00 (N (N to =L ¢0 伽( oo 〇 m um ax3 艇 题 X _ 饀 E- o. ιίτττίΐ Pt] •B- 瘓 κι 饀 驅 99 G〇IB m m m m 湘 败 £3? §s 缠 舞 <itU 碟 狴 繫 雄 貍 sg 1 I 氍 趣 趙 鐽 攝 鐽 m §s 5S 鐽 翳 键 _ m B 链 μ, 魈 涯 « « 糊 猢 氍 饀 繼 <tmi1 _ fr 裝 醒 m m 1 ' II κ IE ffl- r E- 氍 m 祕 饀 mV ΙΠΝ 棚 銻 KI ΐε 魃 裝 Kl 扣 r 联 嵌 勧 m II m m T*WN KI 嵌 -14- 1362926 [表2] 實施例4 比較例4 膏體成份 (w / w % ) 精製水 42.4 1 42.56 甘油 3 9 39 1，3-丁 —醇 3 _ 3 聚丙烯酸 5 5 聚丙烯酸鈉 4 4 羧甲基纖維素鈉 4.3 4.3 羥丙基纖維素 0.5 0.5 二羥基鋁胺基乙酸酯 0.06 0.06 酒石酸 1.5 1 .5 依地酸鈉 0.08 0.08 對羥基苯甲酸丙酯 0.1 對羥基苯甲酸甲酯 0.05 支撐體 ____ 纖維（聚醯胺彈性體） 外觀重量40 g/m2 外觀重量2 g/m2 薄膜（聚醯胺彈性體） 厚度1 5 μπι 厚度1 0 μπι 膏體重量 350g/m2 350 g/m2 [實施例5] 於實施例1製品之軟膏成份配合做爲藥劑之戊酸倍他 米松（0 · 1 w / w % )，作成貼劑。 [實施例6] 於實施例1製品之軟膏成份中配合做爲藥劑之阿昔洛 維（5 w/w%)作成貼劑。 [比較例5] -15- 1362926 配合做爲藥劑之戊酸倍他米松（0.12 w/w%)之軟膏 劑（市販品）。 [比較例6 ] 配合做爲藥劑之阿昔洛維（5 w/w%)之軟膏劑（市 販品）。 [試驗例1] 使實施例1~4及比較例1~4之製品切成7.5cm xlOcm 後，做成試驗例。於3名健康成人男性中，1曰1片試驗 • 劑貼附8個小時，進行觀察貼附中與剝離時之狀況。其試 驗結果如表3所示。 由此試驗結果證明，比較例製品中，貼附時試驗例多 半剝離，且，剝難時，支撐體損壞，產生膏體與支撐體之 分離，或支撐體內之纖維與薄膜間分離，手腕上殘留附著 φ膏體、試驗例等，均不適做爲本發明貼劑。 另外，實施例製品則於貼附時試驗例之剝離，且，剝 離時，極少殘留附著膏體，試驗例於手腕，做爲本發明貼 劑具充功能均爲理想者。 -16- 1362926 【iComparative Example 3 (w/w%) 43.24 Ib - 0.06 (N d (N 〇m 〇 dance 60% 28% 12% | 25 g / m 2 1 ss 3g m Liu 10 μ m rt — 350 g/m" Comparative Example 2 50.44 ο m cs m cs <N 〇0.06 a md 60% 28% 12% 1 18g/mz 1 80 μ m 400 g / mz Comparative Example 1 | 42.44 ON mm 々iTi w-> Ο 0.06 in 100% 1 〇1 3g/m2 1 15 μ m cn — 300 g / m2 Example 3 43.24 沄in 卜m — in (N 0.06 (N iT) d < N dmd 30% 70% 25 g / m ^ | 10 μ m tT ! 230 g/m" | Example 2 50.44 <N ο m fS (N <N d 0.06 a md 鐽<D 50% 50% | l〇g/mJ | HOT m 20 μ m *T) 350 gfm1 NN »Λ v〇yrt ε E m E , deer (N dd S 00 (N (N to =L ¢0 伽( oo 〇m um ax3 boat problem X _ 饀E- o. ιίτττίΐ Pt ] • B- 痪κι 饀 99 G〇 IB Mmmm 湘 败 £3? §s 缠舞<itU 狴 雄 雄 s s s s s s 鐽 鐽 « « « « « « « « « « « « « « « « « « « « « ;tmi1 _ fr awake mm 1 ' II κ IE ffl- r E- 氍m secret mV 锑 shed KI ΐ ε 魃 Kl buckle r 勧 m II mm T*WN KI inlay-14- 1362926 [Table 2 Example 4 Comparative Example 4 Paste composition (w / w % ) Refined water 42.4 1 42.56 Glycerin 3 9 39 1,3-butanol 3 _ 3 Polyacrylic acid 5 5 Sodium polyacrylate 4 4 Sodium carboxymethyl cellulose 4.3 4.3 Hydroxypropyl cellulose 0.5 0.5 Dihydroxy aluminum amino acetate 0.06 0.06 Tartaric acid 1.5 1 .5 Sodium edetate 0.08 0.08 Propyl p-hydroxybenzoate 0.1 Methylparaben 0.05 Support ____ Fiber ( Polyamide elastomer) Appearance weight 40 g/m2 Appearance weight 2 g/m2 Film (polyamide elastomer) Thickness 1 5 μπι Thickness 1 0 μπι Paste weight 350g/m2 350 g/m2 [Example 5] The ointment composition of the product of Example 1 As co-agent of betamethasone valerate (0 · 1 w / w%), made patch. [Example 6] Acyclovir (5 w/w%) as a drug was added to the ointment component of the product of Example 1 as a patch. [Comparative Example 5] -15- 1362926 An ointment (commercially-sold product) of betamethasone valerate (0.12 w/w%) as a pharmaceutical agent. [Comparative Example 6] An acyclovir (5 w/w%) ointment (commercial product) was used as a medicament. [Test Example 1] The products of Examples 1 to 4 and Comparative Examples 1 to 4 were cut into 7.5 cm x 10 cm to prepare test examples. Among the 3 healthy adult males, 1 曰 1 test • The agent was attached for 8 hours, and the condition during the attachment and peeling was observed. The test results are shown in Table 3. As a result of the test, it was confirmed that in the comparative product, the test example was mostly peeled off at the time of attachment, and when the peeling was difficult, the support was damaged, and the separation of the paste from the support was caused, or the fiber and the film in the support body were separated, on the wrist. The residual adhesion φ paste, test examples, and the like are not suitable as the patch of the present invention. Further, the product of the example was peeled off in the test example at the time of attaching, and when the peeling was carried out, the paste was rarely left to adhere, and the test example was applied to the wrist, and it was desirable to perform the filling function of the patch of the present invention. -16- 1362926 [i
No.3 o 靜 yri « •rnS 銮鐽。 淫案键 0 m. o 〇 —-N mm 銮龌 a,騸 雜^ 似一 |譲 °羅° m<km *恶容 銮觀糊I 涅n®銮 伥 返。 鍰渥 μ \fr 。私 _觀 N鄉 丑·銮 忘:黯 g翹迄 f _ 设_ ® mmm 闼恻靆 1塞i ftiS 藍。Λ 0 S鎧*Ν遲 貼附後7小時剝落之。 ^ Rjp S黎 il m3 ， *ί 7·Ν。 '鐽渥 班Φ砟 鋥騮_ 。細 鍵犖 展1 ^ Μ ί喊 mm mm Λ rv ίΐΓ •fr驼迄 銮鍇挪 淫蛾》藍 No.2 m I^JZC Ilf 93 伥 ή 截 Μ 爾0 •Μ砟 銮槲 钿 燄 Ή 伥 鍵 冢‘ mW S® rtr 冢舍 N鯽 fl- Mt h,«7 ο i®? 1迄 2鯽 mm 銮龄 ρ张 mm 冢龌 鈿 m 睬 33 伥 m ®f .莲 鍵\fh Μ ^ •Ν鹳 Ή~ _ 翻 1^1 i Ί鹦 ίΦ& -Ν Hi 。錄由 1：^4< 龄鲣„ Ή概龌 伥銶Φ。 •Β·舞聽溪 藍籍_ \fr 盌騮鄯窀 鍵。 蔟酃 Bm g激 Si 寂蜜 λ啦 •fro mft l| φ H g_ 。容 1® f黎 ^•N 室鍵。 趄Φ蓥 雜蜮 1雜 錯 4t^。 。 鎧迄 醛龌銮 S Φ ® 伥鯽燄 5~_ 蘅 銮球龌 No.l _r Ή 礙 系：。 籍έ mm 。鍵〇 鎧Φ鉴 III 佘泰:k "mm 酒截細 歯鹬^ TO似舰 •frtg 銮錄2 盌菡:S 燄 93 伥 m 4tii 〇 -f 冢鯽 -f\J 0糊1 銮荃 S鈿 囊1 =is ^ He mm 回龄 盌伥 •tf驼。 荃鍰遲 l|i ^ it Hf» mm^ ΐπί · Μ f r».r 麗巧激 讀！S „黯_ s龌·κ 〇 N 按 案 f 七 v〇 S 躞砟 ||l _ mm 。|ι|υ 展1 f£ 荃龌。 每。 |濡 w ik 蔴糊3 。妄 »«··， te^L. _匿 S滅 .」*! · 伥鹦 子雜 Volunteer/試驗劑 m 辑 (N m m w m m 闺 w 寸 镯 * 鎰 (N 匡 鎰 -1J cn m 趦 Ϊα 寸 ΛΛ -17- 1362926 [試驗例2 ] [試驗例2 - 1 ] [試驗方法] 針對乾癣發症患者之病變部位，於左右對稱兩處，以 1天2次，塗佈含去炎松（〇.1 w/w% )軟膏進行2週。其 中1處由所塗佈之軟膏上貼附實施例4之製品後，覆蓋之 後，調整貼附每次所塗佈軟膏。又，另一處以未貼附實施 φ例4之製品進行比較對照之。 進行觀察開始治療4週之間經時性病變部位，依下記 判定基準進行評定之。 [判定基準] [表4] 判定基準①：紅斑等皮膚刺激出現發疹症狀 評分 基 準 症 狀 0 正 常 無 異 常 (無發疹症狀）。 1 輕 度 患 部 稍 出 現 紅 疹。 2 中 度 患 部 出 現 紅 疹 〇 3 重中度 患 部 出 現 極 度 紅疹》 4 重 度 患 部 明 顯 S〇v\ 出 現 紅疹。 [表5] 判定基準②：丘疹等皮膚由周圍隆起之發疹症狀 評分 基準 症狀 0 正常 無異常（無發疹症狀）。 1 輕度 患部稍出現發疹。 2 中度 患部之發疹周圍呈圓狀、或呈傾斜之隆起。 3 重中度 患部之發疹周圍明顯隆起。 4 重度 患部之發疹周圍呈極明顯之隆起。 -18- 1362926 [表6] 判定基準③：鱗屑等皮膚表面粗糙呈發疹症狀 評分 基準 症狀 0 正常 無異常（無發疹症狀）。 1 輕度 鱗屑狀發疹產生覆蓋部份患部。 2 中度 鱗屑狀發疹粗糙狀覆蓋部份患部。 3 重中度 具厚度之鱗屑狀發疹呈粗糙狀、患部全 域被覆蓋之。 4 重度 鱗屑狀發疹厚度極厚、非常粗糙患部全 域被覆蓋之。 評分之計算方法例 評分9 =(判定基準①爲重中度3分+判定基準②爲中度2 分+判定基準③爲重度4分）No.3 o Static yri « •rnS 銮鐽. Episode key 0 m. o 〇 —-N mm 銮龌 a, 骟 ^ ^ Like one | 譲 ° 罗° m<km * 恶 糊 I I I n 銮 。 。 。锾渥 μ \fr . Private _ View N Township ugly 銮 Forget: 黯 g 迄 f f _ Set _ ® mmm 闼恻叇 1 plug i ftiS blue. Λ 0 S铠*Ν Late Peel off 7 hours after attachment. ^ Rjp S Li il m3 , *ί 7·Ν. '鐽渥班Φ砟 鋥骝_. Fine key 荦 1 ^ Μ ί mm mm mm Λ rv ΐΓ ΐΓ fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr fr冢' mW S® rtr 鲫舍N鲫fl- Mt h,«7 ο i®? 1 up to 2鲫mm ρ ρ sheet mm 冢龌钿m 睬33 伥m ®f .Lian key\fh Μ ^ •Ν鹳Ή~ _ Turn 1^1 i ΊPei ίΦ& -Ν Hi. Recorded by 1:^4< Age 鲣 Ή Ή Overview Φ. • Β·舞听溪蓝籍_ \fr Bowl 骝鄯窀 key. 蔟酃Bm g 激Si 寂蜜λ啦•fro mft l| φ H g_容1® f黎^• N chamber key. 趄Φ蓥蓥11 ^ 。 龌銮 龌銮 龌銮 龌銮 龌銮 5 5 5 5 5 5 5 5 : : : : : : : : : : : : έ mm. Key 〇铠Φ鉴III 佘泰:k "mm wine cut fine 歯鹬^ TO like ship•frtg 銮录2 Bowl 菡:S 焰93 伥m 4tii 〇-f 冢鲫-f\J 0 Paste 1 銮荃S 钿 1 1 = is ^ He mm Back to the bowl 伥•tf camel. 荃锾 l l|i ^ it Hf» mm^ ΐπί · Μ fr».r Li Qiao radically read! S „黯_ s龌·κ 〇N According to the case f seven v〇S 躞砟||l _ mm . |ι|υ Exhibition 1 f£ 荃龌. each. |濡 w ik 麻糊3.妄»«··, te^L. _ S S 灭.”*! · 伥 子 杂 Vol Volunteer / test agent m series (N mmwmm 闺w inch bracelet * 镒 (N 匡镒-1J cn m 趦Ϊα inch ΛΛ -17-1362926 [Test Example 2] [Test Example 2 - 1 ] [Test method] For the lesions of patients with dry warts, the lesions were symmetrical two places, twice a day, and coated with triamcinolone (〇) .1 w/w%) The ointment was carried out for 2 weeks, one of which was attached with the product of Example 4 from the applied ointment, and after covering, the ointment applied was adjusted and attached each time. The product of φ Example 4 was attached and compared. The observation was performed on the time-lapse lesions between the four weeks after the start of treatment, and the evaluation was performed according to the following criteria. [Judgement criteria] [Table 4] Judgment criteria 1: Skin such as erythema Stimulating rash symptoms scoring baseline symptom 0 normal no abnormality (no rash symptoms) 1 mild rash in mild affected area 2 rash in moderate affected area 〇 3 severe erythema in moderately affected part 4 severely affected S〇v\ has a rash. [Table 5] Judgment Base 2: Qiu The skin of the rash, such as the rash, is marked by the surrounding rash. The baseline symptom is 0 normal and no abnormality (no rash symptoms). 1 The affected part has a slight rash. 2 The rash around the moderate affected part is round or tilted. 3 The rash around the moderately affected part is obviously bulged. 4 The rash around the severe affected part is extremely prominent. -18- 1362926 [Table 6] Judgment criterion 3: Scaling and other skin surface roughness is the rash symptom baseline symptom 0 Normal and no abnormality (no rash symptoms) 1 Mild scaly rash produces coverage of some affected parts. 2 Moderate scaly rashes cover rough part of the affected area. 3 Heavy moderately scaly rash The rough shape and the affected area are covered. 4 The severe scaly rash is extremely thick and the rough part of the affected area is covered. The calculation method of the score is as follows: 9 (Decision criterion 1 is moderately moderate 3 points + judgment criterion 2 is Moderate 2 points + judgment base 3 is severe 4 points)
[試驗結果] 被驗者 評分（1日） 評分（1週） 評分（2週） 評分（4週） No. 1 8.5/8.5 3.5/8.0 2.5/6.0 2.5/6.0 No.2 6.5/6.0 3.0/5.5 2.0/4.0 6.0/7.0 評分：實施例4製品之貼附被覆/未被覆 [試驗例2-2] 除使用含氯氟美松（0.05 w/w%)軟膏（市販品）之 外，與試驗例2-1同法實施之。 -19- I362926 [表8] 装驗者 評分（1日） 評分（1週） 評分（2週） 評分（4週） --No. 1 5.5/5.5 3.5/4.0 1.5/1 .5 1.0/2.5 ^分：實施例4製品之貼附被覆/未被覆 [試驗例2 - 3 ] [試驗方法] 針對乾癣發症患者之病變部位於左右對稱分爲2處， 針對其中1處，以1天2次，進行塗佈實施例4製品2週 °另一處，未使用軟膏與實施例4之製品，進行比較對照 之》 [表9] [試驗結果1 被驗者 評分（1日） 評分（1週） 評分（2週） 評分（4週） No. 1 6.5/6.5 4.5/6.0 5.0/7.0 5.5/7.0 N 〇. 2 5.0/4.5 3.0/5.5 2.0/5.0 4.5/5.5 評分：實施例4製品之貼附被覆/未被覆 由試驗例2-1及2-2，於疾患部位進行塗佈含藥效成 份之軟膏於皮膚上，藉由貼附實施例4製品，提高治療效 果，且其效果亦持續有效〇又，由試驗例2-3顯示，實 施例4之製品未使用其他軟膏，以單體使用亦有治療效果 因此，本發明貼劑顯現可更提昇含藥效成份基劑之效 力，且，具有做爲薄型化貼劑功能下，即使僅使用單體貼 -20- 1362926 劑亦具理想療效。 [試驗例3] 摘取實驗鼠腹部皮膚裝置於Franz型擴散吸收槽，將 實施例5之製品進行直徑15mm之圓形（含53 gg戊酸倍 他米松）之穿孔試驗劑貼於擴散吸收槽之實驗鼠皮膚上部 。又，將比較例5之44mg軟膏（含53 戊酸倍他米 φ松）塗佈於擴散吸收槽之實驗鼠皮膚上部，針對其半數以 聚酯薄膜覆蓋塗佈軟膏之上面。於接受器側使用30%異丙 醇一磷酸緩衝液，每一固定時間採取接受器液，利用 HPLC，測定採取液中戊酸倍他米松濃度，求取透過實驗 鼠皮膚之藥物量。試驗結果示於第1圖。 由此試驗結果證明，實施例5之製品相較於市販軟膏 劑之比較例5其藥物透光量較高，且與以聚酯薄膜做爲支 撐體被覆之該軟膏劑具同等以上之持久性。 Φ 藉此，顯示本發明貼劑亦有助於具療效藥物（皮質類 固醇劑）之配合。 [試驗例4] 摘取實驗鼠腹部之皮膚裝置於Franz型擴散吸收槽， 使實施例6製品以直徑15mm之圓形（含2.6mg阿昔洛維 )穿孔之試驗劑貼附於擴散吸收槽之實驗鼠皮膚上部。又 ，將52mg比較例6軟膏（2.6mg阿昔洛維）塗佈於擴散 吸收槽之實驗鼠皮膚上部。於接受部側利用磷酸緩衝液， -21 - 1362926 於每固定時間採取接受器液’利用hplc，測定採取液中 阿昔洛維濃度，求出透過實驗鼠皮膚之藥物量。試驗結果 如第2圖所不。 由此試驗結果證明相較於市販軟膏劑之比較例6,實 施例6製之藥物透光量較高，具同等以上之持久性。 藉此顯示本發明貼劑亦有助於具療效藥物（抗病毒劑 )之配合。 [產業上可利用性] 本發明薄型化水性貼劑係利用於絡合天然纖維與軟質 塑膠纖維於支撐體複合纖維中使軟質塑膠樹脂呈薄膜狀所 熱熔接之纖維薄膜，或共有軟質部與硬質部於支撐體之塑 膠所構成之纖維中熱熔接共有軟質部與硬質部之塑膠樹脂 纖維薄膜後，以水、保濕劑、聚丙烯酸衍生物（黏著力增 強劑）、纖維素衍生物（黏著調整劑）、難溶性多價金屬 φ鹽、及pH調整劑做爲必須構成成份之黏著劑用於膏體後 ，可以塗佈量150〜500g/m2進行薄層層合，相較於先行糊 劑，可發揮如下之效果。 ① 具十足的黏著力，貼附部位之活動時隨從性良好， 控制由支撐體之水份的蒸發，因此，可長時間維持皮膚之 保水作用》又，配合藥效成份時，或，藥效成份，抑或使 藥效成份分散、溶解之基劑廣範圍塗佈於皮膚進行貼附後 ’藉由長時間保水作用，提高維持治療效果。 ② 保存中未減少膏體中之水份，且，有效維持黏著力 -22- 1362926 、保形性’因此’可長時間維持安定之品質。 ③降低膏體量’進行薄型化後，適當提昇製造，同時 可降低製造、保管、流通等成本。 【圖式簡單說明】 第1圖係代表戊酸倍他米松之實驗鼠皮膚透光量之圖 者。 第2圖係代表阿昔洛維之實驗鼠皮膚透光量之圖者。[Test results] Subject score (1 day) Score (1 week) Score (2 weeks) Score (4 weeks) No. 1 8.5/8.5 3.5/8.0 2.5/6.0 2.5/6.0 No.2 6.5/6.0 3.0/ 5.5 2.0/4.0 6.0/7.0 Rating: Attachment/Uncovered of the product of Example 4 [Test Example 2-2] Except for the use of clofibrate (0.05 w/w%) ointment (marketed), Test Example 2-1 was carried out in the same manner. -19- I362926 [Table 8] Tester's score (1st) Score (1 week) Score (2 weeks) Score (4 weeks) -- No. 1 5.5/5.5 3.5/4.0 1.5/1 .5 1.0/2.5 ^分: Attachment/Uncovered of the product of Example 4 [Test Example 2 - 3] [Test method] The lesion of the patient with dryness is divided into two places, one for each, one day for one Two times, the product of Example 4 was coated for another 2 weeks, and the ointment was not used and the product of Example 4 was compared and compared [Table 9] [Test result 1 Subject score (1 day) score ( 1 week) Rating (2 weeks) Rating (4 weeks) No. 1 6.5/6.5 4.5/6.0 5.0/7.0 5.5/7.0 N 〇. 2 5.0/4.5 3.0/5.5 2.0/5.0 4.5/5.5 Rating: Example 4 Applying the coated/uncovered test specimens 2-1 and 2-2, applying the ointment containing the medicinal ingredient to the skin at the affected site, and attaching the product of Example 4 to improve the therapeutic effect, and the effect thereof It is also effective and effective. Further, as shown in Test Example 2-3, the product of Example 4 does not use other ointments, and the use of the monomer also has a therapeutic effect. Therefore, the patch of the present invention can enhance the drug content. Ingredients effectiveness of bases, and, as a thin patch having a function, even if the use of only a single agent is also considerate -20-1362926 having the desired effect. [Test Example 3] The abdominal skin device of the experimental mouse was taken out in a Franz type diffusion absorption tank, and the product of Example 5 was subjected to a perforation test agent having a diameter of 15 mm (containing 53 gg of betamethasone valerate) to the diffusion absorption tank. The upper part of the skin of the experimental mouse. Further, 44 mg of an ointment of Comparative Example 5 (containing betahyl pivalate φ pine) was applied to the upper part of the skin of the test mouse of the diffusion absorption tank, and the upper surface of the coated ointment was covered with a polyester film for half of it. A 30% isopropylol phosphate buffer solution was used on the receiver side, and a receiver solution was taken at each fixed time. The concentration of betamethasone valerate in the solution was measured by HPLC to determine the amount of the drug passing through the skin of the test mouse. The test results are shown in Figure 1. The results of the test prove that the product of Example 5 has a higher amount of light transmissive than that of Comparative Example 5 of the commercial ointment, and has the same durability as the ointment coated with the polyester film as a support. . Φ Thereby, it is shown that the patch of the present invention also contributes to the cooperation of a therapeutic drug (corticosteroid). [Test Example 4] The skin of the abdomen of the experimental mouse was taken out in a Franz type diffusion absorption tank, and the test piece of Example 6 was perforated with a circular shape (containing 2.6 mg of acyclovir) having a diameter of 15 mm and attached to the diffusion absorption tank. The upper part of the skin of the experimental mouse. Further, 52 mg of Comparative Example 6 ointment (2.6 mg of acyclovir) was applied to the upper part of the skin of the experimental mouse of the diffusion absorption tank. On the receiving side, a phosphate buffer solution was used, and -21 - 1362926 was taken at a fixed time. Using hplc, the concentration of acyclovir in the liquid was measured, and the amount of the drug passing through the skin of the test mouse was determined. The test results are as shown in Figure 2. As a result of the test, it was confirmed that the amount of light transmitted by the compound of Example 6 was higher than that of the comparative example 6 of the commercial ointment, and the durability was equal to or higher than that of the above. This shows that the patch of the present invention also contributes to the cooperation of a therapeutic drug (antiviral agent). [Industrial Applicability] The thinned water-based patch of the present invention is a fiber film which is obtained by laminating a natural plastic fiber and a soft plastic fiber in a support composite fiber to heat-bond a soft plastic resin into a film form, or a soft portion and a soft portion. The hard part is thermally welded to the fiber composed of the plastic of the support body, and then the plastic resin fiber film of the soft portion and the hard portion is combined with water, a moisturizer, a polyacrylic acid derivative (adhesion enhancer), and a cellulose derivative (adhesive). The adjusting agent), the poorly soluble polyvalent metal φ salt, and the pH adjusting agent are used as an adhesive for the constituent components, and can be applied in a thin layer at a coating amount of 150 to 500 g/m 2 , compared with the prior paste. The agent can exert the following effects. 1 Fully adhesive, the adherence of the attached parts is good, and the evaporation of the water from the support is controlled, so that the water retention effect of the skin can be maintained for a long time", in combination with the medicinal ingredients, or the efficacy Ingredients, or the base agent for dispersing and dissolving the medicinal ingredients can be applied to the skin for a wide range of applications, and the therapeutic effect can be improved by long-term water retention. 2 The water in the paste is not reduced during storage, and the adhesion is effectively maintained. -22- 1362926, conformality 'so' can maintain the quality of stability for a long time. (3) Reduce the amount of paste. After the thickness is reduced, the manufacturing can be appropriately improved, and the costs of manufacturing, storage, and distribution can be reduced. [Simple description of the figure] Fig. 1 is a graph showing the amount of light transmission of the experimental mouse of betamethasone valerate. Figure 2 is a graph representing the amount of light transmitted through the skin of the experimental mouse of acyclovir.
-23--twenty three-